Plant derived or derivable material with appetite suppressing activity

ABSTRACT

A method of suppressing or curbing appetite and treating or preventing obesity comprising administering to a human or other mammal in need of such treatment an effective amount of plant material derived or derivable from plants of the genera  Stapelia  and  Orbea.

This application claims the benefit of U.S. Provisional Application No.60/332,401 filed Nov. 16, 2001, which is hereby incorporated byreference in its entirety.

The present invention relates to plant derived or derivable materialwith appetite suppressing activity.

Despite a rising worldwide epidemic of obesity there is currently only avery small number of anti-obesity drugs available to manage the problem.Behavioral analysis of pharmacological agent-induced anorexia in animalsdemonstrates that various compounds profoundly effect feeding behaviorin differing ways. This indicates the variety of mechanisms by whichpharmacological agents can induce changes in food intake, body weightand eventually body composition. Some of the same pharmacological agentsproduce decreases in food intake and weight loss in humans. Some ofthese pharmacological agents do so by modifying the functioning of theappetite system as measured by subjective changes in feelings of hungerand fullness (indices of satiety). Such pharmacological agents can beconsidered as “appetite suppressants” with clinical potential asanti-obesity agents.

According to the present invention there is provided a method ofsuppressing or curbing appetite comprising administering to a human orother mammal in need of such treatment an effective amount of plantmaterial derived or derivable from at least one plant of the generaStapelia L. and Orbea Haw, hereinafter the plant material of theinvention.

The invention further provides the use of plant material derived orderivable from at least one plant of the genera Stapelia L. and OrbeaHaw in the preparation of a pharmaceutical or nutritional formulationfor suppressing or curbing appetite.

The invention also provides plant material derived or derivable from atleast one plant of the genera Stapelia L. and Orbea Haw for use as anappetite suppressant or appetite curbing.

Also provided is a method of treating and/or preventing obesitycomprising administering to a human or other mammal in need of suchtreatment an effective amount of plant material derived or derivablefrom at least one plant of the genera Stapelia L. and Orbea Haw.

The invention further provides a method of improving the bodilyappearance comprising administering to a mammal a plant material derivedor derivable from at least one plant of the genera Stapelia L. and OrbeaHaw in an amount effective to curb, reduce or suppress appetite andrepeating said administration until a beneficial loss of body weight,e.g., a cosmetically beneficial loss, has occurred.

In another aspect, the invention provides a method for promoting weightloss or maintenance of a desired body weight comprising administering toa human or other mammal in need of such treatment an effective amount ofplant material derived or derivable from at least one plant of thegenera Stapelia L. and Orbea Haw.

In a further aspect of the invention, there is provided a use of acomposition comprising plant material derived or derivable from at leastone plant of the genera Stapelia and Orbea in the manufacture of amedicament, a pharmaceutical composition or a nutritional compositionfor suppressing or curbing appetite, for treating and/or preventingobesity, or for promoting weight loss or maintenance of a desired bodyweight.

The genus Stapelia L. comprises some 50 species occurring naturally intropical and southern Africa and belonging to the family Asclepiadaceae.The genus Orbea Haw comprises some 20 species occurring naturally intropical and southern Africa and also belonging to the familyAsclepiadaceae. Preferred Stapelia species, which are useful for thepurpose of the present invention, include the following: Stapeliagigantea L. and Orbea variegata (L.) Haw. Synonyms used for Orbeavariegata L. include Stapelia variegata L. and Stisseria variegata (L.)Kuntze. Synonyms used for Stapelia gigantea are Stapelia cyclistra,Stapelia marlothii and Stapelia nobilis. Common names of plant speciessuitable for this invention are Starfish flower, (Giant) Toad Plant,Carrion Plant, etc.

This is the first report of an activity on appetite suppressing, curbingor reducing from plants of the genera Stapelia and Orbea.

The plant material of the invention may be prepared from the stemsand/or roots of the plants used according to the invention, hereinafterreferred to as biomass or plant biomass. As used herein, the term “plantmaterial” may refer to one or more of the following: fresh plantmaterial taken directly from the plant without further treatment, driedpowder from the original biomass, sap or dried sap, extracts of biomassor fractions thereof, isolated active compounds and synthetic analoguesof isolated active compounds. Preferably it refers to the dried sap,extracts or fractions of biomass, isolated active compounds andsynthetic analogues thereof.

The plant material may be prepared by one or more of the followingprocesses:

-   -   a) by drying and grinding the original biomass to a dried        powder;    -   b) by pressing the plant biomass, collecting the sap and drying        the sap;    -   c) by preparing extracts of the plant biomass with suitable        solvents, which may be either used as crude extracts or further        fractionated; and    -   d) by isolating pure substances, in particular pregnane        glycosides, from the plant biomass.

A suitable method for drying and grinding the original biomass includeseither sun drying followed by a heated air-drying or freeze-drying,e.g., lyophilization or chopping of the biomass into small pieces, e.g.,2-10 cm, followed by heated air-drying or freeze-drying. Once sufficientmoisture has been removed, e.g., more than 90%, the material can beground to a coarse particle size, e.g., 0.01-1 mm, using a commercialgrinder. For laboratory scale extraction, a coffee grinder or equivalentcan be used.

A suitable method for preparing dried sap includes the steps of pressingcollected plant biomass to separate the sap from solid plant biomass,recovering the sap free of the solid plant biomass, and either dryingthe sap or further purifying it, e.g., by way of suitable extractionprocedures. The sap may be dried by spray-drying, freeze-drying orvacuum-drying, to form a free-flowing powder.

In general terms, a suitable method for preparing an extract of thebiomass of a plant used according to the invention, the extractcomprising an appetite suppressing or curbing agent, comprises the stepsof treating collected plant biomass, with a solvent to extract afraction having appetite suppressant or curbing activity, separating theextraction solution from the rest of the plant biomass, removing thesolvent from the extraction solution and recovering the extract. Theextract so recovered may be further purified by way of suitableextraction or purification procedures.

In a first step, the plant biomass may be ground to a coarse powder orthe sap can be dried to yield a powder, as described above. Subsequentlya suitable solvent may be added to the powder. Suitable solvents includewater, dilute acids, organic solvents, critical, supercritical or nearcritical fluid solvents, e.g., carbon dioxide, nitrous oxide, propane,ethane, ethylene and fluorohydrocarbons, and mixtures of any of these.Organic solvents may include butane, hexane, acetone, methanol, ethanol,propanol, butanol, methylene chloride, dichloromethane, acetonitrile,ethyl acetate, butyl acetate or any mixture thereof. Alcohol-basedsolvents, i.e., pure alcohol solvents and mixtures thereof with water orother organic solvents, are preferred. Ethanol is the most preferredsolvent for the first extraction step.

The extraction solution may then be separated from the residual plantbiomass by an appropriate separation procedure, such as, e.g.,filtration and/or centrifugation. The solvent may be removed, e.g., bymeans of a rotary evaporator. The separated crude extract can then betested to confirm appetite suppressant or appetite curbing activity in asuitable in vivo bioassay.

In a preferred method, the extract is then further fractionated withdichloromethane:methanol:water, e.g., 5:2:3, in a separatory funnel. Theorganic phase is removed and dried, then further fractionated byhexane:methanol:water, e.g., 5:4.5:5. The hexane phase is discarded andthe aqueous methanolic phase is dried by rotary evaporation to yield apartially purified active extract.

The partially purified active extract may be dissolved in methanol, andmay be further fractionated by column chromatography, employing eitherreversed-phase (C18) or normal phase (silica gel) as an adsorptionmedium. A plurality of different fractions may be obtained, and each maybe evaluated, by suitable bioassaying procedures to determine theappetite suppressing or appetite curbing activity thereof.

In one preferred mode of performing the extraction procedure, apartially purified active extract having appetite suppressant orappetite curbing activity is further fractionated, e.g., by columnchromatography using silica gel as an adsorption medium and a 9:1chloroform:methanol solvent, and the resultant subfractions bioassayedfor their appetite suppressant or appetite curbing activity. Asub-fraction displaying appetite suppressant or appetite curbingactivity may, if desired, be further fractionated and purified, e.g.,conveniently using a column chromatographic procedure, e.g., with silicagel as the adsorption medium and a 9:1 ethylacetate:hexane solvent aseluent. The resultant purified fractions may again be evaluated bysuitable bioassay procedures for their appetite suppressant or appetitecurbing activity.

Alternatively, the partially-purified extract or fraction can be furtherfractionated, e.g., by using reversed-phase (C18) HPLC and eluting withwater:acetonitrile (70:30) or similar conditions.

The extract may be dried to remove moisture, e.g., by spray-drying,freeze-drying or vacuum-drying, to yield a free-flowing powder.Optionally, the extract may be dried on a pharmaceutically acceptablecarrier, such as maltodextrin or starch.

The plant material of the invention may also be extracted andconcentrated without drying to give a liquid extract, which is effectivein curbing or suppressing appetite.

A suitable fraction or fractioned extract of a plant used according tothe invention may be prepared by one or more of the following processsteps:

-   -   a) drying and grinding the plant material to a coarse powder;    -   b) extracting the powder with a solvent to form an extract;    -   c) fractionating the extract into a number of fractions;    -   d) concentrating or drying the fractions; and    -   e) selecting those fractions which are effective in suppressing        appetite.

Purified or fractionated extracts may be admixed with any conventionalpharmaceutical excipient, diluent or carrier.

The active extract may comprise one or more compounds isolated from theplant used according to the invention, more preferably from the plantOrbea variegata, such as saponins, e.g., pregnane glycosides, e.g.,stavarosides, more preferably stavarosides A, B, C, D, E, F, G, H, I, Jand K. Pregnane glycosides, which can be used in the present invention,include one or more of the following compounds of formula (I) which canbe isolated from Orbea variegate.

wherein R₁-R₆ have the following meaning: Compound R₁ R₂ R₃ R₄ R₅ R₆Stavaroside A H H H Ang OH H, O-Bz Stavaroside B H H H Ang OH H, O-TigStavaroside C H H O—Ac Bz H ═O Stavaroside D H H O—Ac Tig H ═OStavaroside E H H H Bz OH H, OH Stavaroside F H H O—Ac Ac H ═OStavaroside G H H H Ac OH H, O—Ac Stavaroside H H H OH H H ═OStavaroside I β-D-glc H O-Ang^(a) Bz^(a) H ═O Stavaroside J β-D-glc HO—Ac Bz H ═O Stavaroside K β-D-glc H O—Ac Tig H ═O^(a)Interchangeable.Ac = AcetateAng = AngelateBz = BenzoateTig = Tiglateβ-D-glc = β-D-glucopyranosyl

Methods for isolating these pregnane glycosides, e.g., stavarosides,from Orbea variegata are known to the person skilled in the art. Onesuch method is described in Phytochemistry, Vol. 39, No. 2, pp. 395-403(1995), said method is hereby incorporated by reference.

The synthesis of such pregnane glycosides, e.g., stavarosides, is stateof the art and can, e.g., be carried out by analogous methods asdescribed in WO 98/46243, and incorporated herein by reference in itsentirety.

As used herein, the term “active compound” refers to an active compoundderived, e.g., isolated, from a plant used according to the invention,e.g., pregnane glycosides of formula (I), derivable, e.g., de novosynthesized compound or synthetic analogue of isolated active compoundor any mixtures thereof.

In one aspect, the present invention provides compositions comprising orconsisting exclusively or essentially of a plant material of theinvention, an extract or an active compound as hereinabove described orany mixtures thereof.

A suitable and accepted in vivo model for measuring appetite suppressionor appetite curbing activity in an animal model is described in Example2. A clinically effective and medically approved anti-obesity drug,sibutramine (REDUCTIL®), can be used as a positive control for reductionin food intake in this model. A plant extract previously reported tohave anorectic effects (Trichocaulon piliferum (L.f.) N.E.Br.) alsotests positive in this in vivo assay, and was used as positive controlin Example 2. Positive results from this test model are therefore a verygood indicator of clinical efficacy in the human context.

Alternatively, suppression, reduction or curbing of appetite can beassessed by any of the methods referred to in WO 98/46243 andincorporated herein by reference in its entirety.

The compositions of the invention as described hereinabove, may beadministered under the supervision of a medical specialist, or may beself-administered.

Daily dosage of a composition of the present invention would usually besingle or multiple servings per day, e.g., once or twice daily, e.g.,for acute or chronic use. However, benefit may be derived from dosingregimens that may include consumption on a daily, weekly or monthlybasis or any combination thereof. Administration of compositions of theinvention, e.g., treatment, could continue over a period of days, weeks,months or years, in order, for example, to constantly control theweight, or until a healthy or cosmetically beneficial loss of bodyweight has occurred. Optimally, the composition of the invention isconsumed at least once a day on a regular basis, prior to, i.e., pre- orpost-prandial administration or during a meal. Preferably, thecompositions of the invention may be consumed prior to a meal.

The composition of the invention may be provided a component of a normalmeal, e.g., a nutritional or slimming composition, or dietarysupplement, e.g., in the form of a health drink, a snack or anutritionally fortified beverage, as well as pill, tablet or softgel.When used as a snack or dietary supplement it will preferably beconsumed between or before meals.

Alternatively, the composition of the invention may be provided as ameal replacement, e.g., frozen meals or freeze-dried meals.

Optionally, the composition according to the invention may benutritionally complete, i.e., may include vitamins, minerals, traceelements as well as nitrogen, carbohydrate and fatty acid sources sothat it may be used as the sole source of nutrition supplyingessentially all the required daily amounts of vitamins, minerals,carbohydrates, fatty acids, proteins and the like. Accordingly, thecomposition of the invention may be provided in the form of anutritionally balanced complete meal, e.g., suited for oral or tubefeeding.

The composition of the invention may optionally comprise conventionalfood additives, such as any of emulsifiers, stabilizers, sweeteners,flavorings, coloring agents, preservatives, chelating agents, osmoticagents, buffers or agents for pH adjustment, acidulants, thickeners,texturizers and so on.

Suitable product formats according to the present invention include foodand beverage products, e.g., solid food products, like bars, e.g.,nutritional bars or cereal bars, powdered drinks, dairy products,breakfast cereals, mücesli, candies, confectioneries, cookies, biscuits,crackers, chocolate, chewing-gum, desserts and the like; liquidcomestibles, like soft drinks, juice, sports drinks, milk drinks,milk-shakes, yogurt drinks or soups, as well as pet treats, pet foods,etc.

It may be desirable to provide the active extract or active compound ofthe invention as a low calorie meal replacement or other nutritional orslimming product. In this case the meal replacement or other nutritionalproduct is preferably low fat, i.e., less than about 10 en %, orsubstantially fat-free, i.e., less than about 2.5 en % contributed byfat, such as about 2 en % fat, based on the total caloric content of thecomposition. Suitably, a single serving of a low calorie mealreplacement will have a caloric value of less than about 1000 kcal, andpreferably between about 200 kcal and about 500 kcal. Suitable lowcalorie nutritional or slimming product may include soft drink, such asjuice, smoothie or soy-based drink; or dispersed in foods of any sort,such as dairy bars, snacks, soups, breakfast cereals, mücesli, candies,tabs, cookies, biscuits, crackers, such as a rice crackers; and dairyproducts, such as milk-shake and yogurt drink.

In another embodiment of the invention, Stapelia or Orbea biomass, orthe composition as hereinabove described, may conveniently be providedin conjunction with a high protein diet for weight loss purposes or formaintaining a stable body weight, for instance, as an additive to aprotein-rich slimming milk shake or other beverage. A high protein dietin this context generally means a minimum of 1.25 g protein/kg bodyweight/day.

Compositions suitable for incorporating the plant material, extract oractive compound of the invention include pharmaceutical compositions,nutraceuticals, nutritional compositions, such as dietary supplements,slimming compositions, medical nutrition or functional food. In additionto the plant material, extract or active compound of the invention, thecomposition of the invention may contain at least one pharmaceuticallyor nutritionally acceptable carrier. Suitable delivery vehicles includesachets, soft gel, powders, syrups, pills, capsules, tablets, inhalants,implants, liquid drops, sublinguals, injectables, patches,suppositories, liquids, etc.

The amount and dosage regimen of the composition of the invention to beadministered is determined in the light of various relevant factorsincluding the purpose of administration, the age, sex and body weight ofindividual subject, i.e., inter alia on the severity of the subject'sobesity or overweight.

Preferred delivery formats for the appetite suppressing or appetitecurbing composition of the invention, would be as a dietary supplementcomprising about 5 mg to about 1000 mg, preferably about 10 mg to about500 mg dry weight dosage of a Stapelia and/or Orbea extract, e.g., aspill, tablet or softgel, or comprising about 0.1 wt % to about 10 wt %,preferably about 0.1 wt % to about 5 wt %, more preferably about 0.5 wt% to about 5 wt % of a Stapelia and/or Orbea extract, e.g., as anutritionally fortified beverage, bar or soft chew. A typical dosage ofactive compounds of the invention is about 0.01 mg body weight/day toabout 200 mg/kg body weight/day, preferably about 5 mg/kg bodyweight/day to about 100 mg/kg body weight/day.

An appropriate dosage range would be approximately 100 mg-100 g/kg bodyweight/day, expressed in terms of dry weight of the source plantmaterial (biomass). A suitable daily dosage for an average, e.g., 70 kg,human being is optimally in the range of about 1 g to about 100 g,preferably of about 5 g to about 80 g, and even more preferably of about10 g to about 50 g. A typical consumption extracted material, e.g., thatrecovered from a first ethanolic extraction step, would be about 100 mgdry weight/person/day to about 10 g dry weight/person/day, or about 1 mgdry weight/kg/day to about 200 mg dry weight/kg/day, preferably about 3mg/kg/day to about 125 mg/kg/day. In terms of purified bioactivecompound isolated from Stapelia and/or Orbea, synthetic analogue thereofor de novo synthesized compound, a suitable dosage range is about 0.01mg/kg to about 100 mg/kg body weight/day, preferably about 0.05mg/kg/day to about 10 mg/kg/day. In one aspect of the invention, asuitable dosage range of the active compound is about 0.1 mg/day toabout 2 g/day.

Preferred methods of administration of the compositions of the inventionwould be by any enteral route, e.g., oral, parenterally, e.g.,intravenously, topically, e.g., through use of a skin patch, bydelayed-release mechanisms, e.g., through an implant or patch, or acrossmucous membranes, e.g., by sublinguals or as a suppository.

Oral pharmaceutical or dietary supplement forms may be made byconventional compounding procedures known in the pharmaceutical art,that is, by mixing the active compound of the invention together withedible pharmaceutically acceptable solid or liquid carriers and/orexcipients, e.g., fillers, such as cellulose, lactose, sucrose,mannitol, sorbitol, and calcium phosphates; and binders, such as starch,gelatin, tragacanth, methylcellulose and/or polyvinylpyrrolidone (PVP).Optional additives include lubricants and flow conditioners, e.g.,silicic acid, silicon dioxide, talc, stearic acid, magnesium/calciumstearates and polyethylene glycol (PEG) diluents; disintegrating agents,e.g., starch, carboxymethyl starch, cross-linked PVP, agar, alginic acidand alginates, coloring agents, flavoring agents and melting agents.Dyes or pigments may be added to the tablets or dragée coatings, forexample, for identification purposes or to indicate different doses ofactive ingredient.

In addition to the plant material or active compound of the invention,the composition of the invention may include one or more further activeingredients selected from the following: capsaicine (red pepper); fattyacids, especially linoleic acid (LA) and conjugated linoleic acid (CLA);glycomacropeptide (GMP); Long Chain Triglyceride (LCT); enterostatin;galactose; glucuronic acid; fibers such as pectin, guar gum, incl.partially hydrolysed guar gum, psyllium and β glucan; hydroxycitrate(HCA); citrus; guarana; β hydroxy butyrate; medium chain tryglycerides(MCTs); D-tagatose; Ephedra L., including Ma Huang or Ephedra sinicaRiedl.; ephedrine; caffeine; potato extract; green tea extract;epigallocatechin gallate, or other catechins; peptide D4; vitamins B, Cand/or E; and chromium picolinate. Alternatively, the active extract oractive compound of the invention may be combined with anti-obesity drug,such as sibutramine (REDUCTIL®), or with another plant extract havinganorectic effects, such as Trichocaulon piliferum (L.f.) N.E.Br. Forexample, the composition of the invention may be provided in the form ofa kit for separate, sequential or simultaneous administration inconjunction with anti-obesity drug.

In another aspect of the invention, there is provided a combinedpharmaceutical preparation for simultaneous, separate or sequential usefor the treatment of obesity or overweight comprising active extract oractive compound of the invention and one or more drug(s) for suppressingor curbing appetite.

EXAMPLES Example 1 Preparation of Plant Extracts

Taxonomically identified plant biomass (stems) is freeze-dried andground to a fine powder using a coffee grinder or equivalent.

Extraction procedure: 100 mL of ethanol are added to 10 g of plantpowder and stirred at room temperature for 15 hours. Each sample isfiltered and the extract concentrated to dryness under vacuum. A 250 mgsample is used for testing in a rat satiety model.

A sap (juice) sample is prepared by taking the whole plant material andpressing to remove the sap (juice) from the biomass. The sap is thenfreeze-dried to produce a sample for testing in a rat satiety model.

Example 2 Testing of Plant Extracts

Animals: These studies are conducted with male Sprague-Dawley rats(RA238 strain OFA/IC; IFFA-CREDO, I'Arbresle, Cedex, France). At thetime of arrival the animals weigh 270-290 g and are housed in groups of5 in Macrolone type IV cages prior to the experiment. The animals aremaintained under a 12:12 light dark cycle (lights off at 18:00) in atemperature and humidity controlled environment (21-23° C.; 47%humidity). Three days before the start of an experiment, the animals areweighed and individually housed in Macrolone type IIIA cages andtransferred into the room with the recording devices, which is equallycontrolled for temperature and humidity and in which no other animalsare housed. Normal rat chow pellets (Nafag Ecosan 890, Gossau,Switzerland) and tap water are present ad libitum and are provided bymodified food troughs and drinking spouts, which allow continuousrecording of the food consumed.

Measurement of food intake: The custom made TSE-software Drink/Feed(version 2.16) allows continuous registration of food intake. Foodintake is recorded by continuously weighing the amount of food remainingin a round stainless steel food basket (8 cm in diameter), which offersfood pellets to the animals at a similar position as the original foodtroughs.

Food intake is continuously recorded in 1-hour intervals over the entiretime of an experiment (90-94 hours). A typical experiment starts onMonday at 10 a.m. with a 2-day run-in phase and lasts until Friday 6a.m. (92 hours), i.e., at the end of the dark phase of 4 consecutivedays. Plant extract test substance application is typically performed onWednesday, 2 hours before the onset of the third dark phase.

Experimental design: The following experiments are performed: Theanimals are randomly assigned to groups of 6, which receive eithervehicle (10% Tween 80 in water ad inj. 5 mL/kg) or plant extractdissolved in vehicle (100 mg/kg). After a 2-day, run-in phase, plantextracts are applied 2 hours before the dark phase of the thirdlight-dark cycle. For exact dosing, the weight of each animal isdetermined on the day of the experiment and recorded, together with anyunusual observations, e.g., stressed animals, difficulties with plantextract application, etc.

Data Analysis: Data are presented as mean±SEM. Food intake is displayedcumulatively in 24-hour time intervals to allow easy visualisation ofingestive behavior over an entire circadian cycle and to allow bestcomparison with previously published data. Statistical analysis todetect differences in ingestive behavior between the control group andthe treatment group is performed by 2 way analysis of variance withrepeated measures followed by a Bonferroni correction (RM-ANOVA,Bonferroni; SigmaStat). Three hypotheses are tested by RM-ANOVA: (a) arethe time courses parallel or do they differ in any way over time?; (b)if curves are parallel, is there a difference by a shift of a constantlevel?; and (c) do the curves remain at the same level over time? Thetime interval for the statistical analysis of the data comprised 14hours, i.e., covering the entire dark phase (12 hours) after drugapplication, which occurred 2 hours before dark onset. The maindifferences in food intake are to be expected during this time period.Extending the statistical calculations to 24 hours would make theanalysis less sensitive, because during the additional 10 time pointsthe animals are usually asleep. P values less than 0.05 were consideredto indicate statistically significant differences. * indicatesdifferences at p<0.05; ** indicate differences at p<0.01; *** indicatedifferences at p<0.001.

Results: The results of the appetite suppressing activity are shown inTable 1. Trichocaulon piliferum had been previously described (WO98/46243) to have appetite suppressing activity and served as positivecontrol. It can be seen that extracts of Stapelia gigantea and Orbeavariegata show appetite suppressing activity for up to 14 hours afteradministration of the plant extract. Also the sap of Stapelia giganteashows appetite suppressing activity for up to 8 hours afteradministration of the dried sap. The activity is not dependent on themode of administration (PO or IP). Plants of the genera Ceropegia L.,Rhytidocaulon P.R.O Bally, Tromotriche Haw. and Sarcostemma R.Br. whichbelong to the same family Asclepiadaceae showed no appetite suppressingactivity. TABLE 1 In Vivo Appetite Suppressant Activity ofAsclepiadaceae Admini- Activity at Species stration 100 mg/kgTrichocaulon piliferum PO *** After 14 hours Ceropegia stapeliiformisHaw. PO Inactive Ceropegia aristolochioides Dcne. PO Inactive Cyanchumnodosum (Jum. &H. Perr.) Desc PO Inactive Ceropegia woodii Schltr.Inactive Rhytidocaulon macrolobum Lavranos PO Inactive Stapelia giganteaPO *** After 14 hours Stapelia gigantea IP *** After 14 hours Stapeliagigantea (sap) PO *** After 8 hours Orbea variegata PO *** After 14hours Tromotriche engleriana (Schltr.) Leach PO Inactive Sarcostemmasocotranum Lavranos PO Inactive*** p < 0.001

1. A method of suppressing appetite in a mammal in need thereof whichcomprises administering to said mammal a therapeutically effectiveamount of a plant material from a plant of the genus Orbea.
 2. A methodof controlling obesity in a mammal in need thereof which comprisesadministering to said mammal a therapeutically effective amount of aplant material from a plant of the genus Orbea.
 3. A method of promotingweight loss or maintenance of a desired body weight in a mammal in needthereof which comprises administering to said mammal a therapeuticallyeffective amount of a plant material from a plant of the genus Orbea. 4.The method of claim 1, wherein said plant is Orbea variegata.
 5. Themethod of claim 1, wherein said plant material is sap, a concentrate, anextract, a fraction or an active compound from said plant.
 6. The methodof claim 1, wherein said plant material comprises a therapeuticallyeffective amount of at least one saponin.
 7. The method of claim 1,wherein said plant material comprises a therapeutically effective amountof a stavaroside, wherein said stavaroside is stavaroside A, stavarosideB or stavaroside C.
 8. The method of claim 7, wherein stavaroside isstavaroside C.
 9. The method of claim 5, wherein said plant material isderived from a process comprising treating said plant material with analcohol-based solvent.
 10. The method of claim 9, wherein said alcoholbased solvent is ethanol.
 11. A composition for suppressing appetite ina mammal comprising a therapeutically effective amount of a plantmaterial from a plant of the genus Orbea.
 12. The composition of claim11, wherein said plant material is sap, a concentrate, an extract, afraction or an active compound from said plant.
 13. The composition ofclaim 11, further comprising a pharmaceutically acceptable carrier. 14.The composition of claim 11, further comprising a nutritionallyacceptable carrier.
 15. The composition of claim 12, wherein said plantmaterial is from about 1-100 g dry weight of said plant material perunit dose of said composition.
 16. A method of preparing an appetitesuppressing fraction of a plant of a genus, said genus being Orbea,comprising: a) drying and grinding a plant material from said plant to acoarse powder; b) extracting said powder with a solvent to form anextract; c) fractionating said extract into a plurality of fractions; d)concentration or drying said fractions; and e) selecting from saidfractions any fraction effective for suppressing appetite.
 17. Acomposition prepared by the method of claim
 16. 18. The composition ofclaim 16, wherein said solvent is ethanol.